Intro to Pharamacology Flashcards by Maria Zepeda

study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes

Pharamacology

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what the BODY does to the DRUG
great practical importance in the choice and administration of a particular drug for a particular patient e.g. renal function

Phamokinetics

Comes into play with choosing drug

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what the DRUG does to the BODY
determines the group in which the drug is classified e.g. beta blockers
Like mechanism of action

Pharmacodynamics

Drug to Body, determins class of drugs

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What are the 4 elements of pharmacokinetics?

Absorbtion
Distribution
Metabolism
Excretion
ADME

Metabolims & Excretion are both elemination

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Where do many orally administered medications pass through first after gut?

The liver then into plasma compartment

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What part of the drug can enter the free tissues or site of action receptors?

Only the free drug can exit the plasama compartment

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Injection of the drug into tissue

Intramuscular administration of drug

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Injection of the drug straight into the blood; plasma

Intravenous

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WHat are the 3 routes of drug administration?

Oral
Intramuscular injection
Intravenous injection

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Explain the time course of drug action

Take drug, drug gets absorbed absorption phase
Drug concentration increases to peak
Drug gets distributed around body distribution
Drug is excreted & metabolized elimination phase

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What are the 4 diffrent ways drugs can cross memebranes?

Aqueous diffusion
Lipid Diffusion
Special carries
Endo/Exocytosis

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What kind of drug permeation?

Drugs may diffuse passively through aqueous channels in the intercellular junctions (eg, tight junctions,

Aqueous Diffusion

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What kind of drug permeation

lipid soluble drugs pass through lipid cell membrane

Lipid Diffusion

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What kind of cell permeation?

Drugs with the appropriate characteristics may be transported by carriers into or out of cells

Special Carrier Diffusion

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What kind of drug permeation

Very impermeant drugs may also bind to cell surface receptors (dark binding sites), be engulfed by the cell membrane ____ , and then released inside the cell or expelled via the membrane-limited vesicles out of the cell into the extracellular space____

Endocytosis & Exocytosis

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What 5 thing does the rate and amount of absorbtion of a drug depend on?

Local blood flow at site of admin (more flow= absorb better)
Lipid Solubility (more lipid soluble easier to cross membrane)
Molecular size (smaller passes esier throguh membrane)
Local pH & Drug ionization (ionized drugs will not cross membrane)
Total Surface Area of Absorbtion (More SA beter)

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Where is the primary site of absorbtion for most oral drugs? why?

The small intestine
* It has vili that increase SA for absorbtion

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fraction of unchanged drug reaching the systemic circulation following administration by any route

Bioavailability

Expressed in %

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What is the bioavailibility of oral administered drugs? How about IV?

i.e How much will end up in systemic circulation

Oral= 75% bioavailable
IV= 100% always

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metabolism of orally administered drug in the liver BEFORE it reaches the systemic circulation

First-Pass Effect
First-Pass Elemination

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What is the result of a high first pass effect?

Decreased in bioavailibity
less reaches the systemic circulation

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What Route of Admin?

PROS
* Conveinient
* Large surface area for absorbtion
CONS
* Drug metabolims
* Incomplete absorbtion
* First pass effect
* GI upset

Oral (PO)

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What route of admin?

PROS
* Direct
* No First pass effect
* Slow infessions of rapid onset of action
* Esier to titrate does
CONS
* Req IV acess
* Hard to remove
* Vascular injury

Intravenous IV

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What route of admin?

PROS
* To specific organs; brain & heart
CONS

Intra-arterial

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# What route of admin? **PROS** * Good for depot storage (if oil based) * Rapi onset of action **CONS** * Pain at site of infection

Intra-muscular (IM)

# What route of admin? **PROS** * Non irritating small volumes * Even slow absorbtion * Adrenaline in local anesthetics **CONS** * Paina at site of infection

Subcutaneous (SC)

# What route of admin? **PROS** * Conventiant * Localizied * Limited systemic absorbtion **CONS** * Effects limited to area of application

Topical

# What route of admin? **PROS** * Immediate action in lungs * Rapid delivery to blood * Local or systemic action **CONS** * Must be in gas, vapor, or aerosol form

Inhalation

# What route of admin? **PROS** * Rapid onset of action * No first pass effect **CONS** * Must be lipid soluble

Buccal

# What route of admini? **PROS** * Direct application * rapud onset of action **CONS** * Injection at site of application * Delayed onset of action

Tansdermal

relates the **amount of drug** in the body to the **concentration of drug (C) in blood or plasma**

Volume of Distribution

What does a high volume of distribution signify?

Means that most of the **drug concentration is enteing the extravascular tissue**. | high amount of drug in the body

What affects Vd?

Affected by tissue and plasma binding and to which it binds more strongly too.

What does a low volume od distribution signify?

Most of the drug concentration is in the vascular compartment (blood)

If a drug is highly bound to plasma protien what is trend in VD

Low value of distributuion because it is stuck in the vascular compartment.

What are the ways in which drugs are bound?

1. Free 2. Bound to plasma protiens (albumin(

Why is it **dangerous to administer two drugs** are highly bound to plasma protein?

Discplacement of one or the other drug from plasma protiens can **result in toxicitiy. ** **monitor pt. more**

Only ____ can distribute into tissues and exert its action

free drug

What are some **principles of drug protein binding**

* Affinity of protien binding site (irreverisble?) * Saturation of binding site (highly bound + loose= toxicity) * Decreased albumin concentration (ex. liver faliure) * Competition for binding sites & substrates * Drug interactions

Drug will accumulate until the amount of drug **administered** per unit of time is **EQUAL** to the amount **eliminated** per unit of time Plateu

Steady State Concentration | Plasma concentration are at steady state

At what **halft life does steady** state normally occur?

At about **4-5 half lifes**, plasma concentration **reaches Css** | 90 then 100%

**Single large dose** of druge used to raise the plasma concentration to a therapeutic level more quickly than would occur through repeated smaller doses—helpful when it takes a long time to reach steady-state

Loading Dose

* Most drug dosing regimens * **maintain a steady state of drug** in the body, ie, just enough drug is given in each dose to replace the drug eliminated since the preceding dose

Maintenence Dose

# type of elemination Biotransformation, body making drug more water soluble so it can leave! **lipophillic to hydrophyllic*

Metabolism

There are two phases in the metabolisms P1 & P2 where do they mainly occur?

The liver 2

What is the **first route** of metabolims a drug can take after absorbtion?

Straight through phase 1 and then conjucated in phase 2.

What is the **second route** of metabolims a drug can take after absorbtion?

Enters phase one and splits into * Drug metabolite with modified activity * Inactive drug metabolite They then anter phase 2 and conjugate

What is the **third route** of metabolims a drug can take after absorbtion?

It can go straight through phase 1 and 2 and striaght to elemination. Excreted unchanged in the urine.

# metabolism What are the **3 elements of Phase 1** and what is the **main purpose?**

1. Oxidation 2. Reduction 3. Hydrolysis **Increasing water solubility of the drug for excretion**

How does **phase 1** of metabilims increase water solubility?

By adding or unmasking a polar functional group *OH, −NH2, −SH*

# Metabolism What enzymes mediate Phase 1?

Cytopchrome p450 liver enzymes

# Metabolism What is the most common Cytochrom p450 enzyme that mediates phase 1 of metabolism?

**CYP3A4** | other Isoforms of Cytochrom P450

# Metabolism What reaction occurs in Phase 2?

Conjucation reactions

# Metabolism When an **endogenous substrate**, combines with newly added functional group to form a **highly polar functional group** | glucuronic acid, sulfuric acid, acetic acid, or an amino acid

Phase 2 of Metabolism | Further increases water solubility and elimination

Why do we look at all the isoforms of Cytochrom P450?

Use of drugs can induce or inhibit certain isoforms.

# Result from? * Increased **synthesis** or decreased rate of degradation of p450 * **Accelerates metabolism of drug** * Results in **decreased effect** * May **increase toxicity of drugs** that are transformed to reactive metabolites

Induction of the Cytochrome 450

# Results from? * Bind to p450 enzyme (sometimes irreversibly) * **Decreases metabolism of drug** or endogenous substances * Results in **increased effect/toxicity**

Inhibition of Cytocrhome 450

**Amiodarone** is an inhibitor of CYP2C9 and CYP3A4 which **inhibits the metabolism of Warfarin** which does what?

**Increases the risk of bleeding** caused by elevted levels of Warfarin in the body

**Carbamazepine** is an inducer of CYP3A4 which **induces more metabolims of oral contraceptives** which does what?

**Increases risk of unplanned pregnancy** caused by decreaed levels of the oral contraceptive (metabolized!)

# metabolism what are the 6 phase two reactions?

1. Methylation 2. Sulfation 3. Acetylation 4. Glucoronidation 5. Glucothionine Conjucation 6. Glycine Conjucation | MSA-GGG

# Elimiation 2. What are the 3 main routes of **excretion**

**KIDNEY** 1. Glomerular filtration 2. Tubular secretion 3. Passive Excretion

If somthing is **not very water soluble** where will it most likely be excreted out of?

**Biological stool**

Why do you have to be cautious when administering drugs to a pregnant newly birthed mother?

Drugs can be excreted through breast milk!

# Elemination rate Estimates in creatine clearence (CrCl)

Cockroft-Gault equation | Depends on renal function

indicates the **time** required to attain **50% of steady state**—or to **decay 50% from steady-state** conditions.

Half Life | Useful in designing drug dosage regimines

EX. half life is 10 hours. * How long to reach stead state? * How long to eliminatr?

* 40-50 hours for both either way

What is the goal of eleminatinon?

goal of metabolism is to **de-toxify drugs**, and make them either **more water soluble** (for excretion in the urine) or **more fat soluble** (for excretion in the bile, and then into the feces).

**any substance that brings about a change in biologic function** through its chemical actions

Drug

**target molecule** in the biologic system that plays a regulatory role

Receptor

a compound that **binds to a receptor** and produces the biologic response by activating the receptor

Agonist

a compound that **binds to a receptor but does not activate** generation of a signal

**Antagonist** Interferes with the agonist ability to activate the receptor, **doesnt generate a signal, no effects on its own, simply a stop**

Explain a competative antagonist

**Maximal effect reached** but at higher doses of agonist The **agonist and antagonist compete** for site of receptor but the **antagonist is not covalantely bound** so it comes off and allows for agonist binding.

Explain non-competative agonist

**Reduced maximal effect** even at high doses of agonist * Irreverisble * Allosteric

Explain mechanism of **irreversible** non-competative inhibitor

The **antagonist covalantely bonds to the receptor site** blocking agonist and there **lowering max effect**

Explain mechanism of **allosteric** non-competative inhibitor

The **antagonist binds to site that is not the receptor**, changing the shape of receptor site and **preventing binding of agonist. **

# Drug Receptor interaction Much more rapid maximal effect

* Agonist * Allosteric activator

# Drug Receptor interaction Normal response

Only an Agonist

# Drug Receptor interaction Delayed incresed, but eventually reaches maximal effect (still less)

* Agonist * Compentative inhibitor

# Drug receptor interaction Drug never reaches the steady state

* Agonist * Allosteric Inhibitor

produces the biologic response but **cannot produce 100%** of the response even at high doses

Partial Agonist | Some designed on purpose.

What is an example when you prescribe a partial agonist?

Trying to get some one off opiod addiction, does not provide the high but also prevents withdrawls.

____ Agonist that have the oppiste effects from a full agonist **decrease basline receptor**

Inverse Agonist

What are the 3 drug receptor bonds

1. Covalent (strong) 2. Electrostatic (weak) 3. Hydrophobic (weakest)

# What bond? **very strong** and in many cases not reversible under biologic conditions

Covalent

# What bond? **weaker then covalent bonds and more common** vary from relatively strong linkages between permanently charged ionic molecules to weaker **hydrogen bonds** and very weak induced dipole interactions such as **van der Waals forces**

Electrostatic

# What bond? **usually quite weak** important in the interactions of **highly lipid-soluble drugs** with the **lipids of cell membranes**

Hydrophobic

Drugs that bind through **weak bonds** are more ____ than drugs that bind in **strong bonds.**

**weak bonds= selective drug** * weak bonds require precise fit